title: Molecular background of urate transporter genes in patients with exercise-induced acute kidney injury.
abstract: OBJECTIVE
  Exercise-induced acute renal failure [exercise-induced acute kidney injury (EI-AKI)] is defined as AKI due to heavy anaerobic exercise. Although hypouricemia is known to be a risk factor for the onset of EI-AKI, a direct causal link between EI-AKI and serum uric acid has not been established. This study aimed to analyze urate transporter genes in patients with EI-AKI and its molecular mechanism.
  
  
  METHODS
  Genomic DNA and total RNA were isolated from peripheral blood leukocytes of patients with a history of EI-AKI. Mutations were analyzed by PCR and a direct sequencing method. We first analyzed the SLC22A12 gene, and then the SLC2A9 gene if no mutations were found in SLC22A12.
  
  
  RESULTS
  Seventeen patients were enrolled in this study and 16 had mutations: 15 in SLC22A12 and 1 in SLC2A9. Fourteen (82.4%) patients showed hypouricemia, and all of the patients with hypouricemia had either homozygous or compound heterozygous mutations in SLC22A12 or SLC2A9, which confirmed that all of them had renal hypouricemia. Two patients had heterozygous mutations of SLC22A12, and they were not accompanied by hypouricemia. One patient was found to have no mutations in SLC22A12 or SLC2A9.
  
  
  CONCLUSIONS
  We were able to determine the genetic background of urate transporter genes in patients with EI-AKI. Decreased function of urate transporters, rather than decreased serum uric acid levels, may be of great importance for the onset of EI-AKI.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.forename: Shingo
authors.initials: S
authors.lastname: Ishimori
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shima
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D002648:Child; D015444:Exercise; D005260:Female; D016678:Genome; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014527:Uric Acid / Q000097:blood; D014545:Urinary Calculi / Q000235:genetics*; D055815:Young Adult
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C411811:SLC2A9 protein, human; C103862:urate transporter; D014527:Uric Acid